Friday, December 3, 2010

Nemeroff and Schatzberg's “Textbook” Pushed Paxil

So I finally got the book, ripped open the manila envelope from an Amazon reseller, and found out exactly what a $120,000 “unrestricted educational grant” will buy: an advertisement for Paxil. Not obvious, not blatant. But artfully crafted, subtle, smooth—more in the style of Nemeroff than Schatzberg. Nemeroff was clearly the mentor in this project.

Much ink has been spilled about whether the book was or wasn’t ghostwritten by a PR firm called STI. This letter from STI to Dr. Nemeroff appears to be a smoking gun of evidence, yet Nemeroff, Schatzberg, and the American Psychiatric Association vehemently deny that this was ghostwritten. (Read the APA's denial here). Rumor has it that Schatzberg is sicking his attorneys on anyone who dares to suggest what seems to be crystal clear based on the documents. But who cares, really? If it was ghostwritten, that's unethical. If it wasn't ghostwritten, it's actually worse for these academics--because the final result is such a finely crafted piece of promotion that any reputable "author" should be embarrassed and ashamed. This is truly a case of "damned if you do, damned if you don't."

You open the book, and the first thing that slaps your retina is a chapter on anxiety disorders. I’ve read a lot of psychiatry textbooks, probably over a hundred, and I can confidently report to you that I have never seen a textbook on general psychiatry (whether written for psychiatrists or PCPs) that begins with a big honking chapter on anxiety disorders. Most begin with tips on diagnosis, basic principles of psychopharmacology, mood disorders, or other topics. But they never begin with anxiety disorders.

How could this possibly matter, you might ask? Because in 1999, the book's publication date, Paxil was in the midst of a blockbuster sweet spot, buoyed particularly by FDA's 1999 approval of the drug for social anxiety disorder. Like all good drug reps, Nemeroff & Schatzberg lead with their product's strength. Thus, on page 18, we hear the rather startling statement that "social anxiety disorder is the most common anxiety disorder and the third most common psychiatric disorder in the US, preceded only by depression and alcohol dependence." That's based on a credulous acceptance of the inflated 13% prevalence figure for social anxiety that was published in 1994. This figure was also the basis of the famous "1 out 8 people have social phobia" line parroted by SmithKline Beecham in their marketing material at the time. Two pages later readers are reassured that there exists a solution to this public health catastrophe: "Currently, only one antidepressant (paroxetine) is FDA approved for the treatment of social anxiety disorder."

Does this prove blatant bias? Is it deceptive? No on both counts. It just lays the groundwork, softening the mark, as a drug rep would say. The entire first chapter is positioned front and center as a way of creating a platform for a series of boasts about Paxil's efficacy. Someone made the decision to organize the book this way, and someone had a reason to do so.

The actual deceptions begin in the chapter on antidepressants on page 77. Here's where Nemeroff and Schatzberg educate PCPs about the confusing array of antidepressants available. Then and now, if you were to ask your average psychiatrist how he or she chooses an SSRI, you would hear that they are equally effective, but that they differ based on side effect profiles. And since the late 1990s, it has been generally acknowledged that the SSRI with the most troublesome side effects is Paxil.

But not according to Nemeroff and Schatzberg's Paxil-funded textbook. Taking a break from the world of general scientific knowledge, this chapter says, essentially, that all SSRIs have some side effects, and that any differences among them are minor.

For example, both Prozac and Paxil have long been known to increase the levels of other drugs that patients may be taking. This is called "drug-drug interactions." In 1999, Paxil and Zoloft reps were sniping at one another over this issue. Zoloft reps were crowing about how "dirty" Paxil was, pointing out that Zoloft, at usual doses, caused hardly any drug drug interactions. Paxil reps, for their part, were desperately trying to downplay this.

So how do Nemeroff and Schatzberg handle this issue? They create Table 47 on page 85, entitled “Common Drug Interactions with SSRIs”. Here, there is no distinction between Paxil and Zoloft. A primary care doctor would falsely conclude that there was no reason to favor Zoloft over Paxil in patients also taking medications like propranolol or Vicodin or amitryptyline. Based on this deceptive table, they might well have favored that wonderful anti-social anxiety drug, Paxil--with potentially serious medical consequences for their patients.

Interestingly, several years later, when Nemeroff was paid by a different drug company, he had a financial incentive to play up Paxil’s drug interaction liabilities. In this CME article funded by Bristol-Myers Squibb to push their antidepressant EMSAM, here’s what Nemeroff and his co-authors had to say about SSRIs and drug interactions: "Not all antidepressants affect CYP enzymes. Antidepressants that do not substantially inhibit any CYP enzyme at their usual therapeutic doses include the SSRIs citalopram, escitalopram, and sertraline [Zoloft];… fluoxetine and paroxetine [Paxil] at 20 mg/day produce approximately a 500% increase in the AUC of CYP2D6 dependent drugs.” This article was eventually cited by ACCME as being blatantly biased in favor of EMSAM, and the company that produced it promptly went out of business.

Not only did Nemeroff and Schatzberg omit data about Paxil's drug interaction dangers, they also neglected to discuss data available in 1999 showing that Paxil caused more sexual dysfunction, more weight gain, and more sedation than other SSRIs.

To sum up, in 1999, Nemeroff and Schatzberg published a textbook called "Recognition and Treatment of Psychiatric Disorders: A Psychopharmacology Handbook for Primary Care." It was funded by SmithKline Beecham with a $120,000 "unrestricted educational grant." Documents posted on the internet hint strongly that the book was ghostwritten by a PR firm hired by the drug company. And an analysis of the book's content shows that it was crafted to encourage primary care doctors to prescribe Paxil preferentially over its competitors, such as Zoloft.

This is yet another heaping of shame upon psychiatry. Rather than sending bullying lawyer letters to whistleblowers, I suggest that the authors issue the following statement: "We hereby apologize to the medical community and to the public for having published this textbook. In 1999, financial relationships with the pharmaceutical industry of this type were considered acceptable. In retrospect, by having legitimized what was essentially a promotional document for SmithKline Beecham, we realize that we did a disservice to the physicians who read the book, and who falsely assumed that the information was objective. We, in conjunction with the American Psychiatric Association, officially retract this textbook in its entirety."

37 comments:

Retraction? Won't ever happen. These people do not possess the necessary psychic equipment for a retraction or an apology.

Meanwhile, where does the figure $120,000 come from? Was it paid directly to Nemeroff? How much did the 'authors' skim from the $120,000? That would be over and above the $18,000 they collected in royalties.

thank you, Dr. Carlat. This is very helpful in trying to understand and as a non-medical person, it would be painful for me to try to wade through the textbook. But what I don't understand is how on earth the APA thinks their protestations are going to be taken seriously given Nemeroff's history??? Bernard Carroll makes a good point too...the $18K was looking kind of paltry, but indeed, who got the $120K?

I agree you've done a great job and as someone who lost a daughter to a Paxil caused drug interaction in 2002, I of course hope that everyone who reads this realizes that these deceptions are not just minor ethical lapses, but actual grounds for criminal responsibility. There are consequences to real live patients of lying about or ignoring what drugs really do.

Yet the bad guys are successful and wealthy and happy. Probably fly first class from one lecture hall to another, take vacations on some beautiful island and dine at the finest restaurants.

Just try to tell anyone that SSRIs are pretty worthless and that trials and publications are distorted, and you'll get The Look. I doubt any of us awake people are going to get rewarded for it in this lifetime, and since I believe this is all there is...

Oh yeah, we got integrity...

This is the most twisted and corrupt profession, void of any true content, and IMO 99% of psychiatrist are eager and willing participants.

I don't know...two-three people are sitting here and discussing this. Some of us have been trying to speak up for years. To no avail. No one is listening. Trough's too full and brainwashing is too strong.

I received my training at Stanford, under the reign of Schatzberg et al, and this makes me wonder if I should reject everything I learned there.

I'm only half joking. If this kind of cr*p went on there, then what am I supposed to think about the influential lectures I heard from other faculty (Schatzberg's cronies) about the wonders of Geodon, Abilify, and Cymbalta, to name three drugs for which I recall very memorable lectures while working on G2 and H2 (the inpatient psych units)? Were these lecturers also bought & paid for by Pfizer, BMS, and Lilly?

The whole thing makes me sick to my stomach. I went there with an open mind and I'm beginning to think it was filled with marketing, not science.

My daughter was treated by Stanford doctors shortly after this monkey business was going on. I'm sorry to be unleashing this bitterness in this forum, but my daughter was a Stanford graduate and a shining light. She should not be dead. The doctors there should be prosecuted. I really believe that. Instead they are still practicing their "medicine" according to exactly the same paradigms they used on her. I did what I could to bring some awareness to the innocents working there, but the corruption in the field is so pervasive it was a pretty useless exercise. And she has not been the only victim either. Again I apologize if I am offending some of you. This is all happening because of forces and trends much bigger than any one of us can really control.

Sara, I am so very sorry for your loss, and as you said, she is not the only tragic loss due to Paxil, not by a long shot. Pacificpsych, I do have had the repeated experience of suggesting the SSRIs are fairly worthless and get The Look, too. Some excellent books out there this year: The Emperor's New Drugs, Anatomy of an Epidemic, and Manufacturing Depression, just to name three. And, oh yeah, somewhere I saw a picture of the home Nemeroff purchased in Miami; quite the pad. He sure doesn't seem to be suffering for his crimes.

Whoever did the original writing and whoever did the editing is not nearly as important as what the book actually said. Bottom line: the book was endorsing and pushing Paxil without the slightest nod to its serious problems with drug interactions, dependency, and withdrawal even though these things had been observed in clinical trials. It came out shortly before the mainstream media was being flooded with an ad campaign for Paxil, the theme of which was "Your life is waiting." Paxil was chosen as the darling drug after 9/11 and suddenly anxiety disorders were pushed into the forefront. How convenient. This really was not science. It was heavy duty marketing. Little details about exactly who did what and when are hardly relevant to the bigger picture of what was going on here.

Thank you for your telephone call in response to my query about sales of a book “Recognition and Treatment of Psychiatric Disorders: A Psychopharmacology Handbook for Primary Care” by Charles Nemeroff, MD, and Alan F. Schatzberg, MD, published by American Psychiatric Publishing, Inc., in 1999. I want to find out the extent of the book’s sales.

As you know, The New York Times had an article, “Drug Maker Wrote Book Under 2 Doctors’ Names, Documents Say,” by Duff Wilson, published on November 29, 2010. The article is available at (www.nytimes.com/2010/11/30/business/30drug.html?_r=1).

According to the article, Ron McMillen, chief executive of American Psychiatric Publishing, which published the book, explained that the book sold about 26,000 copies, including 10,000 bought by SmithKline Beecham and 10,000 bought by Organon. The authors together received a 15 percent royalty of the $120,000 sales, or about $18,000.

If book sales were $120,000, and 26,000 copies were sold, then the book sold for only about $4.65. Could it be that total sales were $1,200,000, for $46.50 per book? Or perhaps only 2,600 books were sold, with only 1,000 to each of the 2 pharmaceutical companies?

According to a book review by Dr. Robert Cancro in Am J Psychiatry 158:331, February 2001 (http://ajp.psychiatryonline.org/cgi/content/full/158/2/331), the book's price was $35.00.

I ask that you check on the numbers of copies sold to the drug companies and others; the dollar amounts of sales and of royalties; and the price of the book.

As I explained, I inquire on my own behalf. I am a freelance medical writer-editor who is deeply concerned about ethics in preparing articles for publication. For example, I refer to AMWA Ethics FAQs (www.amwa.org/default.asp?id=466), which I wrote for the American Medical Writers Association.

Meanwhile, I have another question: When did American Psychiatric Publishing first become aware that Drs. Nemeroff and Schatzberg had relationships with Scientific Therapeutics Information and with SmithKline Beecham in relationship to development of the book, “Recognition and Treatment of Psychiatric Disorders: A Psychopharmacology Handbook for Primary Care"?

Thank you for your telephone call in response to my query about sales of a book “Recognition and Treatment of Psychiatric Disorders: A Psychopharmacology Handbook for Primary Care” by Charles Nemeroff, MD, and Alan F. Schatzberg, MD, published by American Psychiatric Publishing, Inc., in 1999. I want to find out the extent of the book’s sales.

As you know, The New York Times had an article, “Drug Maker Wrote Book Under 2 Doctors’ Names, Documents Say,” by Duff Wilson, published on November 29, 2010. The article is available at (www.nytimes.com/2010/11/30/business/30drug.html?_r=1).

According to the article, Ron McMillen, chief executive of American Psychiatric Publishing, which published the book, explained that the book sold about 26,000 copies, including 10,000 bought by SmithKline Beecham and 10,000 bought by Organon. The authors together received a 15 percent royalty of the $120,000 sales, or about $18,000.

If book sales were $120,000, and 26,000 copies were sold, then the book sold for only about $4.65. Could it be that total sales were $1,200,000, for $46.50 per book? Or perhaps only 2,600 books were sold, with only 1,000 to each of the 2 pharmaceutical companies?

According to a book review by Dr. Robert Cancro in Am J Psychiatry 158:331, February 2001 (http://ajp.psychiatryonline.org/cgi/content/full/158/2/331), the book's price was $35.00.

I ask that you check on the numbers of copies sold to the drug companies and others; the dollar amounts of sales and of royalties; and the price of the book.

As I explained, I inquire on my own behalf. I am a freelance medical writer-editor who is deeply concerned about ethics in preparing articles for publication. For example, I refer to AMWA Ethics FAQs (www.amwa.org/default.asp?id=466), which I wrote for the American Medical Writers Association.

Meanwhile, I have another question: When did American Psychiatric Publishing first become aware that Drs. Nemeroff and Schatzberg had relationships with Scientific Therapeutics Information and with SmithKline Beecham in relationship to development of the book, “Recognition and Treatment of Psychiatric Disorders: A Psychopharmacology Handbook for Primary Care"?

Important work nicely done, Daniel. As someone else said somewhere about this — can't recall — it takes the breath away. And as Drummond Rennie said to me once about this basic dynamic, 'That's not medicine. That's marketing."

This is egregious, and it's easy to be discouraged. However, it's my take, following this for several years now, that watchdogging such as yours and the advocacy and educational efforts done by people such as Sara Bostock HAS had an effect, and that while some docs and pharma companies still work the old way, many docs are more skeptical of pharma claims and adjust their practices accordingly. I know from personal contacts that many prominent psychiatrists are far more aware of these problems than were five years ago, and as a whole, the field has a sharper awareness of conflicts of interest, of the dangers of overprescribing, and of the weakness of the evidentiary database supporting the broad use of these drugs. Many are changing their prescription practices. The work is not in vain.

To provide funds for an initial print run of the book (more than likely the 10,000 that SKB picked up, by their own admission) would probably have run around $50-60K ten years ago. $18K, from what I understand, went to Schatzberg and Nemeroff. The remainder was STI's fee for their services, most likely the writers whose names have been all over the news, plus any account managers responsible for the project. Just needed to clear that up, as some misinterpretations have been flying around about that figure being related to book sales, etc.

Am I wrong to note this, or didn't Dr Schatzberg go on to be APA President within the past couple of years? What does this say about the majority of APA members, that majority being those who voted for him, if I am correct?

As George Carlin noted about politicians and what really sucks about politics, it is not the KOLs who are corrupt who are the problem, but, those who listen to every word like gospel, even after the corruption is exposed.

Neither one of these "gentlemen" have souls, but what about those in the company they keep? Why do these two people continue to write and give CMEs? And why do physicians of alleged responsible reputation go to them!?

I love this quote from fellow Healthy Skepticism member Andrew Herxheimer:

"The notion of 'opinion leader' and 'key opinion leader' has developed into a commercial euphemism popular with people planning drug promotion. It would be useful to try to replace it, at least in part, by more transparent terms, e.g. opinion carrier pigeons, opinion carriers, opinion messengers, opinion transporters, opinion agents.

We probably needn't go as far as opinion dummies or opinion tarts. How about collecting all our ideas and then voting on them? Let's try to pinion the worst leading opiners."

Great article by Dr Carlat. The book itself does show the authors are damned either way.

I and some other colleagues have given presentations on the often unethical nature of Pharma-Medicine relationships at conferences and grand rounds - what is really noticeable is a sea-change (at least here in Australia) amongst psychiatrists in the way they think about and relate to Pharma and the too often Marketing-based literature that masquerades as Evidence-based. Now when giving such talks the audience is invariably totally onside. I think a much overdue paradigm shift back towards a more holistic psychiatry is underway.

Also Pharma are businesses, it is hard and financially foolish for them in a free enterprise competitive market to be openly scientific. It is us psychiatrists, our journals and our institutions who must create the necessary distance between us and Pharma for science and ethical practice to occur.

Oh and "Pharma Whores" is a more commonly used term one hears bandied about now at conferences than those other suggestions.

Paxil was suggested by my primary care physician for my atypical depression shortly after this was published. Within 3 days I felt better than I had in my entire life to that point. That led to a referral to a gastroenterologist and an eventual diagnosis of an atypical gluten enteropathy. While it may have been promoted by big pharma and may have harmed some people, Paxil was a godsend for me.

To the Anonymous who wrote that Paxil helped enormously, can you clarify whether you meant it was prescribed 3 days after this post was published or 3 days after the book was published? If your correct diagnosis was gluten enteropathy how was Paxil helping with that? I lost you somewhere in the middle of your comment. If you've just recently gone on Paxil, then I would just like to caution you that you are in a so called honeymoon period and I would advise you to do some internet searching on Paxil withdrawal to see just how long you really want to stay on it. Good Luck.

I've been taking paxil since 1993 and I'm pretty sure it helps. I take so much other stuff, though, it's hard to say if it's the paxil or the lithium or the seroquel or the... I haven't tried to kill myself lately, but then again no command voices have been telling me what to do. I don't dare miss doses because the withdrawals are horrible. My psychiatrist won't discontinue it because she insists I need to continue taking it. So here I am...forever on paxil.

I got my 31¢ copy of the Nemeroff Schatzberg book today, and can confirm Danny's read as above about the Paxil bias. But he left out an important point. It's an insultingly simplistic book. I was frankly shocked that anyone would think it might be useful - freebie or not.

That's because you weren't the target audience. The target audience was the primary care doc who doesn't have the time to do a thorough psychosocial assessment, get a complete history, evaluate the treatment options, etc., and for that reader, the authors (whoever they were) only needed to make one point:

The spectral fingerprints of a big drug company have once again been found all over academic publications. Documents released last week by a watchdog group based in Washington DC raise concerns about the role of writers paid by GlaxoSmithKline (GSK) in works attributed to psychiatric researchers at a number of US institutions. They add to the drumbeat of allegations in recent years indicating that such ghostwriting — in which articles contain substantial portions written by someone who is not listed as an author — is endemic in the biomedical literature.

The documents were made available as a result of litigation over GSK's antidepressant Paxil (paroxetine) and were pounced on by the Project on Government Oversight, which raised concerns about authorship of a research article, journal editorial and textbook.

The researchers did acknowledge the alleged ghostwriters of the textbook and the editorial in notes, but only for “editorial support”. For the journal article, which appeared....

I received a reply from the Communications Office of the American Psychiatric Association to my questions, posted previously, about the extent of sales about the book, “Recognition and Treatment of Psychiatric Disorders.”

I am with the communications office at the APA. Your questions were forwarded to me, and I have gotten information from the publisher.

To answer your first question, the publisher said most of the sales were bulk sales, which come in around $4-5/copy, so your calculations were correct.

It's been more than a decade since this work was done, and no one who was involved in the project is still employed by American Psychiatric Publishing; but their records show the publisher knew early that there was an unrestricted educational grant and that STI was providing appropriate editorial support-not ghostwriting.

Recognition and Treatment of Psychiatric Disorders: A Psychopharmacology Handbook for Primary Care, by Charles B. Nemeroff, MD, PhD, and Alan F. Schatzberg (1999), was, according the introduction, “designed to provide primary care physicians with brief, practical information on the pharmacologic treatment of psychiatric disorders in adults.” Although I do not know if the book’s design met its intention, the book was clearly useful for medical writers who needed a quick introduction to psychiatric disorders and their pharmaceutical treatment. An updated edition would be really useful.

As the introduction explains, the first of two main sections, “Overview and Pharmacotherapy of Psychiatric Disorders”, provides a short description of the epidemiology, pathophysiology, presentation, diagnostic criteria and screening tools, and step-by-step approaches such as treatment algorithms. Thus, the first section sorts by disorder and consider drugs to treat them. Then in what is an excellent stroke of organization, the other main section, “Psychopharmacologic Agents,” reverses the order by sorting by drugs and then considering the disorders that they treat. This section reviews basic pharmacology, pharmacokinetics, drug interactions and safety concerns, and dosing. Each section works well by consistently applying formulaic, consistent organization. The book’s glossary is helpful, as is the appendix containing selected diagnostic rating scales. The book’s overall design makes it easy to use.

I loved every word in this book. But given the disturbing concerns in the book’s development, and Dr. Carlat’s expert description of the book’s deceptions, I don’t trust any word of it.